Genetic and cellular characterizations of human TCF4 with microsatellite instability in colon cancer and leukemia cell lines

被引:5
作者
Chang, HR
Cheng, TL
Liu, TZ
Hu, HS
Hsu, LS
Tseng, WC
Chen, CH
Tsao, DA
机构
[1] Fooyin Univ, Dept Med Technol, Kaohsiung 831, Taiwan
[2] I Shou Univ, Dept Biomed Engn, Kaohsiung 840, Taiwan
[3] Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol, Kaohsiung 807, Taiwan
[4] Chang Gung Univ, Grad Inst Med Biotechnol, Taoyuan 333, Taiwan
[5] Chung Shan Med Univ, Inst Biochem & Biotechnol, Taichung 402, Taiwan
关键词
TCF4; microsatellite instability; leukemia;
D O I
10.1016/j.canlet.2005.03.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It has been reported that the mutational inactivation of the adenomatous polyposis coli (APC) and beta-catenin genes play important roles in colorectal carcinogenesis. However, alteration of the components in the Win signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has been elucidated. To define the precise role of the Wnt signaling components in CRC and leukemia cell lines with MSI, mutational analyses of the T cell factor 4 (TCF4) genes were performed. Here we describe for the first time a TCF4 MSI + phenotype in leukemia cell lines except in colon cancer cell lines. Moreover, we found that these cell lines exhibited deletion and insertion of 1-2A in an (A)9 repeat so as to result in (A)7, (A)8 (A)10 and (A)11 repeat, respectively. To characterize the cellular function of these special TCF4 mutant clones, transient transfection and fluorescent microscopy were analyzed and the results revealed that the TCF4 frameshift gene products all localized in nuclei. Surprisingly, these TCF4 frameshift mutants lost transcriptional activity with beta-catenin and down-regulate the target gene expression. These results delineate a novel role for MST+ TCF4 in leukemia and colon cancer progression. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:165 / 171
页数:7
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